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Abstract

Endothelial cells’ (ECs’) mitochondrial redox equilibrium may become disturbed, which can lead to persistent inflammation and atherosclerosis. Endothelial dysfunction can be brought on by oxidative damage amplified by chronic sympathetic hyperactivity. We tested whether renal denervation (RDN), a technique for lowering sympathetic tone, can protect ECs by reducing the inflammation caused by mitochondrial reactive oxygen species (ROS) to prevent atherosclerosis.

Before consuming a high-fat diet for 20 weeks, RDN or a sham procedure was performed on ApoE-deficient (ApoE/) mice. The EC phenotype, atherosclerosis, and mitochondrial morphology were identified. To ascertain the mechanisms behind RDN-repressed endothelial inflammation, human artery ECs were given norepinephrine treatment in vitro. RDN decreased inflammation, oxidative stress, and atherosclerosis in EC mitochondria. The persistent sympathetic hyperactivity raised the activity of the enzyme monoamine oxidase A (MAO-A) and the amount of norepinephrine in the blood. impaired MAO- The production of atherogenic and proinflammatory molecules was increased in ECs as a result of ROS buildup and NF-B activation caused by the activation of mitochondrial homeostasis. Additionally, it inhibited PGC-1, a regulator of mitochondrial function, with the help of NF-B and oxidative stress. The inhibition of EC atheroprone phenotypic changes and atherosclerosis was achieved by disrupting the positive-feedback regulation between mitochondrial dysfunction and inflammation caused by the inactivation of MAO-A by RDN.

Keywords: Renal denervation, Endothelial dysfunction, Mitochondrial dysfunction, Inflammation, Atherosclerosis